DCTN1 mutations in Perry syndrome

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Farrer M. J., Hulihan M. M., Kachergus J. M., Dachsel J. C., Stoessl A. J., Grantier L. L., ...More

NATURE GENETICS, vol.41, no.2, pp.163-165, 2009 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 41 Issue: 2
  • Publication Date: 2009
  • Doi Number: 10.1038/ng.293
  • Journal Name: NATURE GENETICS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.163-165
  • Hacettepe University Affiliated: Yes

Abstract

Perry syndrome consists of early-onset parkinsonism, depression, severe weight loss and hypoventilation, with brain pathology characterized by TDP-43 immunostaining. We carried out genome-wide linkage analysis and identified five disease-segregating mutations affecting the CAP-Gly domain of dynactin (encoded by DCTN1) in eight families with Perry syndrome; these mutations diminish microtubule binding and lead to intracytoplasmic inclusions. Our findings show that DCTN1 mutations, previously associated with motor neuron disease, can underlie the selective vulnerability of other neuronal populations in distinct neurodegenerative disorders.